Divergent regulation of vascular endothelial growth factor and of erythropoietin gene expression in vivo

There is accumulating evidence from in vitro experiments that the gene expression of the vascular endothelial growth factor (VEGF) is, like that of the erythropoietin (EPO) gene, regulated by the oxygen tension and by divalent cations such as cobalt. Since the information about the regulation of VEGF gene expression in vivo is rather scarce, this study aimed to examine the influence of hypoxia and of cobalt on VEGF gene expression in different rat organs and to compare it with that on EPO gene expression. To this end male Sprague-Dawley rats were exposed to carbon monoxide (0.1% CO), hypoxia (8% O₂ ) or to cobalt chloride (12 and 60 mg/kg s.c.) for 6 h. mRNA levels for VEGF- 188, -164, and -120 amino acid isoforms in lungs, hearts, kidneys and livers were semiquantitated by RNase protection. For these organs we found a rank order of VEGF mRNA abundance of lung >> heart > kidney = liver. EPO mRNA levels were semiquantitated in kidneys and livers. Hypoxia, CO and cobalt increased EPO mRNA levels 60-fold, 140-fold and 5-fold, respectively, in the kidneys, and 11-fold, 11-fold and 3-fold, respectively, in the livers. None of these manoeuvres caused significant changes of VEGF mRNA in lung, heart or kidneys. Only in the livers did hypoxia lead to a significant (50%) increase of VEGF mRNA. These findings suggest that, in contrast to the in vitro situation, the expression of the VEGF gene in normal rat tissues is rather insensitive to hypoxia. In consequence, the in vivo regulation of the VEGF and the EPO genes appear to differ substantially, suggesting that the regulation of the VEGF and EPO genes may not follow the same essential mechanisms in vivo. Received: 31 July 1995/Received after revision: 20 November 1995/Accepted: 27 November 1995     

Change of surgical treatment in benign thyroid gland diseases-- influence of surgical management on perioperative complications

Since the beginning of 1994 standardized primary radical resection was performed in benign thyroid diseases at the surgical department, Barmherzige Brueder Hospital, Graz. In multinodular euthyroid goiter bilateral lobectomy or near total lobectomy respectively was done. In case of Graves' disease unilateral lobectomy and contralateral near total resection or "en bloc" thyroidectomy was performed. In accordance with literature a significant reduction of recurrent laryngeal nerve paralysis from approximately 9% to 1.2% occurred in our patients if this surgical procedure was performed consequently. Hypocalcemia rate after surgery needing treatment was approximately 1% at the time of demission.     

Fibrous histiocytoma: a histological and statistical analysis of 155 cases.

Various salient histological features were rated from + to +++ in a semiquantitative evaluation of a series of 155 cases of fibrous histiocytoma. Relations between individual histological features, as well as between histological findings, localisation and size of lesions, and age or sex of the patient were tested statistically. Most impressive was an inverse proportional relationship between cellular and fibrillar densities: highly cellular fibrous histiocytomas chiefly showed little fiber formation. Accordingly, cases with marked fiber formation were distinguished by low cellularity. Based on this statistically significant relation, 3 subtypes could be classified on a scale of increasing fiber formation and decreasing cellular density. The majority of cases showed medium cellularity and fibrillar density, with distinct storiform (spokewheel or "whirlygig") pattern which is compatible with typical storiform histocytoma, including clincally progressive, recurrant FH and/or "dermatofibrosarcoma protuberans". The typical patient was more frequently female than male, 40 years of age with a 0.5 to 1.0 cm size tumor node in the lower extremities located in the corium, often with beginning infiltration of the subcutaneous fat tissue.     

Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

 As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions, application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens, immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative. In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. Conclusions: The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression, but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty. Accepted: 29 September 1997     

Transsexual development after committing an offense

Connections between transsexualism and delinquency have been considered in only a few publications to date. The authors report on a forensic psychiatric case with a transsexual development after committing an offence based on sexual deviations. Transsexualism in this context seems to represent an attempt for the symbolic solution of a conflict of identity. This should be interpreted in the context of psychotherapy and not be misunderstood as a symptom proving the diagnosis of manifest transsexualism by orientation on pure phenomenological criteria.     

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. Received: 8 March 1999 / Final version: 25 May 1999     

Incudostapedial joint in health and disease.

The incudostapedial joint was studied in tomograms of 370 normal and 80 diseased middle ears. The Guillen view was found to be superior to the anteroposterior view in demonstrating this joint in normal middle ears (85% and 62% visualization, respectively). In the presence of disease, visualization was markedly reduced to 19%; this lack of visualization is a nonspecific finding since early cholesteatomas, chronic otitis media, and retraction pockets could not be differentiated radiologically. Nonvisualization of the incudostapedial joint in the Guillen view is a more objective indicator of middle ear disease than such terms as "indistinct of hazy" middle ear cavities.     

Metastasiertes osteosarkom mit undifferenzierten karzinomähnlichen anteilen

Zusammenfassung Es wird über ein Osteosarkom bei einem 64jährigen Mann berichtet, bei dem aufgrund des Biopsiebefundes mit undifferenzierten Tumoranteilen sowie auch wegen des Alters and des Röntgenbefundes an Karzinommetastasen im Knochen gedacht wurde. Ein Primartumor konnte jedoch nicht gefunden werden. Die Autopsie ergab ein z.T undifferenziertes karzinomähnliches, daneben jedoch deutlich tumor-, knochen- and knorpelbildendes Osteosarkom im Bereich des linken Hüftgelenks mit multiples Skelettund Lungenmetastasen, ohne daß dabei trotz hohem Alter and ausgedehnter Ausbreitung des Sarkoms ein M. Paget als Vorerkrankung oder Risikofaktor nachgewiesen werden konnte.

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Summary This was the case of a 64-year-old man with osteosarcoma. The biopsy yielded undifferentiated tumor without bone or cartilage formation. Because of high age of the patient and radiological changes present, a metastatic carcinoma was suspected. However, no primary could be found. Autopsy revealed an osteosarcoma in the region of the hip joint with alternating formation of tumor cartilage and tumor bone. There were also undifferentiated portions of endocrine osteosarcoma, simulating carcinoma. In spite of extensive skeletal involvement and pulmonary metastases-and high age-no evidence of morbus Paget of bone as possible preneoplastic disease was found.